All patients with systemic mastocytosis have elevated plasma histamine levels. These plasma histamines remain consistently elevated over a 24-hour period. No diurnal variation was noted. Patients with urticaria pigmentosa have normal or slightly elevated plasma histamines, while patients with idiopathic anaphylaxis show elevations in plasma histamine during attacks of anaphylaxis. Plasma histamine elevations in subjects with systemic mastocytosis are not affected by antihistamines (chlorpheniramine and cimetadine), cromolyn sodium, or prednisone. Plasma histamines correlate with disease severity as assessed by bone scan. Two forms of mastocytosis have been documented. Ninety percent of our patients have disease presenting initially as urticaria pigmentosa and which slowly progresses over decades. A second rapidly progressive form of mastocytosis presents with lymphodenopathy and peripheral eosinophilia. Human bone marrow cultured in the presence of lectin-induced lymphocyte-derived growth factors yield increased numbers of mast cells/basophils after several weeks in culture. Human peripheral mononuclear cells produce factors which stimulate the division of mouse mast cells.